Triethylamine → HCID 178496598, compound

Participants

Reaction Steps

2-(1H-Imidazo[4,5-b]pyridin-6-yl)-9-(cis-4-methoxycyclohexyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxamide. 1-((Z)-2-Amino-1,2-dicyanovinyl)-3-(cis-4-methoxycyclohexyl)urea (See example 160.B) (375 mg, 1.42 mmol), 1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-b]pyridine-6-carbaldehyde (See example 130.C) (644 mg, 2.80 mmol), triethylamine (0.4 mL, 2.80 mmol) and methanol (20 mL) were reacted according to General Procedure B. The solution was allowed to stir at room temperature overnight and the resulting precipitate was collected by filtration to give 9-(cis-4-methoxycyclohexyl)-8-oxo-2-(1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-b]pyridin-6-yl)-8,9-dihydro-7H-purine-6-carboxamide. This THP-protected intermediate (235 mg, 0.48 mmol) was dissolved in dioxane (2 mL) and a 4.0 M HCl/dioxane solution (4.0 mL) and water (0.3 mL) were added. The resulting solution was stirred at room temperature overnight. The reaction was neutralized with saturated sodium bicarbonate, extracted with EtOAc (3×50 mL), and pooled organics were dried over sodium sulfate. The crude product was purified via reverse-phase semi-prepatory HPLC (20-100% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). The volatiles were removed under reduced pressure, treated with saturated sodium bicarbonate and extracted with ethyl acetate (3×75 mL). Organic layers were pooled, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting solid was washed with diethyl ether and dried in a vacuum oven at 60° C. overnight to afford the title compound (15 mg, 0.036 mmol, 7.5%) as a white solid. 1H NMR (400 MHz, MeOD-d3) δ 9.56 (s, 1H), 8.50 (m, 1H), 7.80 (m, 1H), 4.31 (m, 1H), 3.51 (m, 1H), 3.39 (s, 3H), 2.77 (m, 2H), 2.07 (m, 4H), 1.53 (m, 4H); MS (ESI) m/z 409.0 [M+1]+; mp 360° C. dec.

Provenance & Evidence